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Biomedical subjects

A Anzueto

Publications and source records attributed to A Anzueto.

At least 55 records · Page 3Linked to original sources
PubMed1997

Effects of continuous bed rotation and prolonged mechanical ventilation on healthy, adult baboons.

OBJECTIVE: To study, in a model of prolonged mechanical ventilation, the role of continuous bed rotation on lung function and pathology. DESIGN: Prospective animal study. SETTING: Animal research laboratory. SUBJECTS: Healthy adult baboons (Papio cynocephalus), anesthetized with ketamine, sedated, paralyzed, mechanically ventilated for 11 days, and monitored with pulmonary and peripheral arterial catheters. INTERVENTIONS: Animals were divided into two experimental groups: a) mechanical ventilation alone (control, n = 7); and b) mechanical ventilation with continuous bed rotation therapy to 45 degrees (continuous rotation group, n = 5). Mechanical ventilation was provided for 11 days with an FIO2 of 0.21 and tidal volume of 12 mL/ kg. Bronchoalveolar lavage was performed through a fiberoptic bronchoscope. Nursing care procedures, antacids, enteral feeding, and prophylactic antibiotics were administered. MEASUREMENTS AND MAIN RESULTS: Measurements of hemodynamics, pulmonary functions, lung volumes, arterial blood gases, and chest radiographs were done daily. Bronchoalveolar lavage was performed at days 0, 7, and 11. There were no significant changes in hemodynamics, gas exchange, or pulmonary functions during the study period in either group. Microbiological surveillance cultures were negative in both experimental groups. In the control group after 7 days, six of seven animals developed patchy atelectasis; by day 11, two of seven animals demonstrated persistent radiologic abnormalities. Bronchoalveolar lavage neutrophils were significantly increased in control animals at days 7 and 11. Lung pathology in the control group showed areas of bronchiolitis, with surrounding bronchopneumonia in five of seven animals. None of the continuous rotation animals showed any radiologic or morphologic abnormalities. CONCLUSIONS: Prolonged mechanical ventilation in the control group resulted in atelectasis, increased concentrations of bronchoalveolar lavage neutrophils, and mild pneumonitis. These effects were not associated with changes in lung volumes, oxygenation, or hemodynamic parameters. Continuous bed rotation helped to prevent these abnormalities.

Animals↗
PubMed1996

Aerosolized surfactant in adults with sepsis-induced acute respiratory distress syndrome. Exosurf Acute Respiratory Distress Syndrome Sepsis Study Group.

BACKGROUND: Patients with acute respiratory distress syndrome (ARDS) have a deficiency of surfactant. Surfactant replacement improves physiologic function in such patients, and preliminary data suggest that it may improve survival. METHODS: We conducted a prospective, multicenter, double-blind, randomized, placebo-controlled trial involving 725 patients with sepsis-induced ARDS. Patients were stratified according to the risk of death at base line (indicated by their score on the Acute Physiological and Chronic Health Evaluation [APACHE III] index) and randomly assigned to receive either continuously administered synthetic surfactant (13.5 mg of dipalmitoylphosphatidylcholine per milliliter, 364 patients) or placebo (o.45 percent saline; 361 patients) in aerosolized form for up to five days. RESULTS: The demographic and physiologic characteristics of the two treatment groups were similar at base line. The mean (+/- SD) age was 50 +/- 17 years in the surfactant group and 53 +/- 18 years in the placebo group, and the mean APACHE III scores at randomization were 70.4 +/- 25 and 70.5 +/- 25, respectively. Hemodynamic measures, measures of oxygenation, duration of mechanical ventilation, and length of stay in intensive care unit did not differ significantly in the two groups. Survival at 30 days was 60 percent for both groups. Survival was similar in the groups when analyzed according to APACHE III score, cause of death, time of onset and severity of ARDS, presence or absence of documented sepsis, underlying disease, whether or not there was a do-not-resuscitate order, and medical center. Increased secretions were significantly more frequent in the surfactant group; the rates of other complications were similar in the two groups. CONCLUSIONS: The continuous administration of aerosolized synthetic surfactant to patients with sepsis-induced ARDS had no significant effect on 30-day survival, length of stay in the intensive care unit, duration of mechanical ventilation, or physiologic function.

Administration, Inhalation↗
PubMed1996

Systemic availability of itraconazole in lung transplantation.

Systemic availability of itraconazole in lung transplantation was evaluated by serially measuring the bioactivity of itraconazole in lung transplant patients who received itraconazole for prophylaxis (n = 12) or therapy (n = 5). These patients also received concomitant antacid and H2 blocker therapy. In patients receiving itraconazole at 200 and 400 mg/day, the median concentrations in serum were 0.5 microgram/ml (range, < 0.05 to 2.7) and 3.5 micrograms/ml (< 0.5 to 14), respectively. The concentration following administration of 400 mg/day was > 2.5 micrograms/ml in 56% of samples, while only 4% of samples from patients who were administered 200 mg/day had levels over 2.5 micrograms/ml. This study documents that itraconazole can be absorbed in patients receiving concomitant antacid and H2 blocker therapy. However, the reduced and variable absorption suggests the importance of confirming drug delivery by measurement of concentrations in serum.

Absorption↗
PubMed1994

Effects of hyperoxia on rat diaphragm function.

The association of oxygen radical generation with impaired diaphragm performance has previously been reported after inspiratory resistive loading (IRL). We hypothesized that exposure of rats to normobaric hyperoxia (O2) could produce impaired diaphragm function because of free radical production. Sprague-Dawley rats were divided into four groups: 1) room air (control), 2) > 95% O2 for 24 h, 3) > 95% O2 for 48 h, and 4) > 95% O2 for 60 h. Each group was studied at rest after the O2 exposure and then after IRL. During IRL, the animals breathed through an inspiratory resistor until they were unable to sustain > 70% of the maximum airway pressure. Diaphragm samples were obtained for analysis of glutathione (GSH) and glutathione disulfide (GSSG) concentrations. In vitro isometric contractile properties were also determined, including maximal tetanic tension (Po) and maximal twitch tension (Pt), in GSSG content and in GSSG-to-GSH ratios. Hyperoxia for > 48 h resulted in significant decreases in Po and Pt and an increase in GSSG content and in GSSG-to-GSH ratios compared with other groups. Those same animals subjected to IRL showed a further decrease in Po and Pt. These data suggest that free radical generation may occur in the diaphragm during a hyperoxia exposure associated with activation of the GSH redox cycle and impairment of diaphragm function.

Airway Resistance↗
PubMed1994

Buthionine sulfoximine treatment impairs rat diaphragm function.

Activation of the glutathione (GSH) redox cycle with production of glutathione disulfide (GSSG) has been shown to occur in the diaphragm during inspiratory resistive loading (RB). Buthionine sulfoximine (BSO) lowers tissue GSH by irreversibly inhibiting the rate-limiting synthesis enzyme gamma-glutamylcysteine synthetase. We investigated the effects of BSO on rat diaphragm function, both at rest and after a period of RB. Rats in the RB groups underwent inspiratory RB until they were unable to sustain 70% of their maximal airway pressure. A portion of the diaphragm was analyzed for GSH and GSSG levels, and measurements of in vitro contractile properties included contraction times, maximal tetanic tension (Po), maximal twitch tension (Pt), and force frequency curves. BSO treatment produced a profound depletion of diaphragmatic GSH. Neither BSO nor RB alone significantly altered diaphragm contractile properties at this load of RB. But, in BSO-RB rats, there was a significant decrease in Pt, Po, and tetanic tension at all frequencies of stimulation compared with those in other groups. These data reveal that animals treated with BSO followed by inspiratory resistive loading exhibit marked diaphragm impairment, suggesting that GSH may play an important role in protecting the diaphragm from the stress induced by this resistive breathing protocol.

Analysis of Variance↗
PubMed1994

Medium term functional results of single-lung transplantation for endstage obstructive lung disease.

Controversy has surrounded the use of single-lung transplantation (SLT) for the treatment of endstage obstructive lung disease. In recent years, several transplant centers have performed SLT for such indications. In this report, we describe functional results in patients undergoing SLT for obstructive lung disease, twenty-two followed over one year and 10 over two years. Data include pulmonary function testing, gas exchange, quantitative ventilation and perfusion to the lung graft, and results of symptom-limited graded cycle exercise testing after SLT. Our results show improvement in obstructive dysfunction FEV1 0.49 +/- 0.13 L (16 +/- 4% predicted) pre-SLT to 1.71 +/- 0.43 L (57 +/- 12% predicted) 3 mo after SLT, FEV1/FVC 0.30 +/- 0.07 pre-SLT to 0.75 +/- 0.09 3 mo after SLT, and improvement in arterial oxygenation, PaO2 58 +/- 10 mm Hg pre SLT to PaO2 86 +/- 13 mm Hg 3 mo post-SLT. In addition, these improvements were sustained up to 1 to 2 yr post-SLT. The majority of ventilation and perfusion go to the new lung graft. After SLT, patients have reduced maximum oxygen consumption (VO2max 40 to 60% predicted) but do not have ventilatory limitation to exercise and can carry out daily activities without compromise. We conclude that SLT is a viable medium-term therapeutic option for endstage obstructive lung disease. The long-term future of this technique remains to be determined.

Adult↗
PubMed1994

Single lung transplantation in patients with systemic disease.

OBJECTIVE: To report functional results and survival in patients undergoing single lung transplantation (SLT) for pulmonary involvement associated with systemic disease or prior malignancy, criteria traditionally considered contraindications to SLT. DESIGN: Case series. SETTING: The University of Texas Health Science Center at San Antonio. PATIENTS: Nine patients who have undergone SLT for end-stage lung disease: four patients with sarcoidosis; two patients with limited scleroderma; and three patients with prior malignancies (two with prior lymphoma and bleomycin-induced pulmonary fibrosis and one who received two bone marrow transplants for acute lymphocytic leukemia and subsequently developed chemotherapy-induced pulmonary fibrosis). MEASUREMENTS: Pulmonary function testing, exercise oximetry, quantitative ventilation-perfusion lung scanning. Actuarial survival. RESULTS: All patients had marked improvement in pulmonary function, exercise oximetry, and quantitative ventilation perfusion to the SLT. One patient with scleroderma died 90 days postoperatively from Pseudomonas pneumonia with a sepsis syndrome. One patient with sarcoidosis died 150 days postoperatively from disseminated aspergillosis. At autopsy, there was no evidence of recurrent fibrosis or sarcoidosis in the transplanted lungs in either of these two patients. The seven surviving patients have returned to work or school and are conducting all activities of daily living without pulmonary disability. The 1- and 2-year actuarial survival rates in these nine patients is 68.6 percent as compared with the 1- and 2-year actuarial survival rates of 66.3 percent and 55.8 percent in the remainder of our SLT group as a whole (n = 49). Despite pharmacologic immunosuppression, there is no evidence of recurrent malignancy in the 3 patients with prior malignancies. CONCLUSIONS: We conclude that carefully selected patients with end-stage lung involvement related to systemic disease or chemotherapy-induced fibrosis may benefit from SLT.

Adult↗
PubMed1994

Use of the flow-volume loop in the diagnosis of bronchial stenosis after single lung transplantation.

Bronchial complications, including stricture, stenosis, and/or anastomotic dehiscence, are a major cause of morbidity following single lung transplantation. This report describes a 19-year-old man with a diagnosis of end-stage pulmonary fibrosis secondary to prior chemotherapy for non-Hodgkins lymphoma who underwent single lung transplantation. The immunosuppressive regimen included cyclosporine, azathioprine, and methylprednisolone sodium succinate (Solu-Medrol) intravenously for six doses during the first 3 days postoperatively followed by oral prednisone. Sixteen weeks following transplantation, the patient complained of dyspnea. Spirometry revealed a decrease in FEF25-75 and the flow-volume curve demonstrated a bioconcave appearance. The flow-volume loop showed a relatively high initial flow phase occurring over the first 2 to 3 s followed by a low-flow phase. The expiratory phase also showed the same characteristics. Bronchoscopy revealed 75 percent stenosis of the bronchial lumen to the transplanted lung. A transbronchial biopsy specimen obtained at that time was consistent with acute rejection. The patient was treated with a methylprednisolone bolus. A repeated bronchoscopy showed the persistence of stenosis distal to the anastomosis. The patient underwent several bronchoplastic balloon dilatations without complete resolution of the stenosis and a stainless steel mesh stent was placed. Repeated spirometry showed marked improvement of the FEF25-75 and normalization of the flow-volume loop. We conclude that the flow-volume loop curve is a noninvasive procedure that may help monitor the patency of the bronchial anastomoses following single lung transplantation.

Adult↗
PubMed1993

Diaphragmatic function after resistive breathing in vitamin E-deficient rats.

The effects of vitamin E deficiency on diaphragm function were studied at rest and after resistive breathing (RB) in Sprague-Dawley rats (wt 300-400 g). The animals were pair fed a vitamin E-deficient diet (E-def) or a matched vitamin E-sufficient diet (E-suf). Each diet group was then further subdivided into a group that breathed unimpeded (control) and a second group that breathed through an inspiratory resistor until the animals were unable to sustain 70% of their maximum airway pressure. Diaphragm samples were obtained for analysis of thiobarbituric acid-reactive substances, glutathione (GSH) concentrations, and glutathione disulfide (GSSG) concentrations. In vitro isometric contractile studies were also performed and included twitch (Pt) and maximum tetanic (Po) tensions, force-frequency curves, fatigue index, and recovery index. Pt was significantly reduced in the E-suf RB group as well as both of the E-def groups. Po was also significantly reduced in both E-def groups. The E-def rats subjected to RB showed a significant decrease in tension at both high and low frequencies compared with the E-suf rats. Concentrations of diaphragm thiobarbituric acid-reactive substances were significantly increased in both E-def groups. RB in both E-suf and E-def rats resulted in increases in diaphragm concentrations of GSSG and decreases in the GSH/GSSG ratios. We conclude that reduction of contractile function, lipid peroxidation, and activation of the GSH redox cycle occur with RB and that these effects are significantly increased in the presence of vitamin E deficiency.

Animals↗
PubMed1993

Diethylmaleate produces diaphragmatic impairment after resistive breathing.

Formation of oxygen-derived free radicals and activation of the glutathione (GSH) redox cycle has been associated with impaired rat diaphragm performance. Diethylmaleate (DEM) given intraperitoneally irreversibly conjugates with GSH, resulting in marked decreases in tissue concentrations of GSH. We have investigated the effects of acute GSH depletion by DEM on diaphragmatic function during resistive breathing (RB) in the rat. The experimental groups were 1) control, 2) DEM alone, 3) RB, and 4) DEM with RB (DEM + RB). RB was obtained by inspiratory RB until the rats were unable to sustain 70% of maximum airway opening pressure. A portion of the diaphragm was frozen for biochemical assays, and the rest of the diaphragm was prepared for measurement of in vitro contractile properties, including maximum tetanic tension, twitch tension, force-frequency curves, and contraction times. DEM treatment produced a profound depletion of GSH in the DEM and DEM + RB groups. Neither DEM nor RB alone significantly altered diaphragm contractile properties. In DEM + RB rats, however, there was a significant decrease in maximum tetanic tension, twitch tension, and tetanic tension. These data reveal that DEM produced an acute depletion of GSH in the diaphragm without impairment of the muscle in nonstressed rats. In the presence of DEM-induced GSH depletion, RB did result in marked diaphragm impairment. The depletion of GSH and the subsequent impairment in diaphragm contractility after RB suggest that GSH may play an important role in protecting the diaphragm against oxidative stress associated with RB.

Animals↗
PubMed1993

Graft position and pulmonary function after single lung transplantation for obstructive lung disease.

Single lung transplantation (SLT) has become a therapeutic option for the treatment of end-stage obstructive lung disease. Between January 1989 and June 1990, there were 14 patients with end-stage obstructive lung disease who underwent SLT. Eleven of these patients were surviving at 1 year following transplantation. Three of the patients had received left-sided SLT, and eight had received right-sided SLT. In the patients receiving left-sided SLT, the native right lung radiographically appeared to compress the left lung graft. In the patients receiving right-sided SLT, the native left lung did not appear to compress the right lung graft. We hypothesized that right SLT may provide a functional advantage over left SLT for patients with obstructive lung disease. We compared pulmonary function test results before and after transplantation (approximately 3 and 12 months) and compared quantitative ventilation-perfusion lung scan results between the patients with left SLT and those with right SLT. Additionally, we compared graded-exercise test results at 3 and 12 months after transplant between the two groups. Our data revealed no statistical difference in pulmonary function test results or graded-exercise test results between the two groups, although patients undergoing right SLT showed greater increases in FEV1 and forced vital capacity than those undergoing left SLT. Quantitative ventilation and perfusion were greater to the graft in patients receiving right-sided SLT than in patients receiving left-sided SLT, most likely due to the larger size of the right lung. We conclude that there is no functional difference between patients undergoing left or right SLT for end-stage obstructive lung disease.

Adult↗
PubMed1992

Resistive breathing activates the glutathione redox cycle and impairs performance of rat diaphragm.

Free radical activation and lipid peroxidation have been described in skeletal muscle during strenuous exercise. We hypothesized that oxygen radicals could also be formed in the diaphragm muscle during strenuous resistive breathing and that these radicals might affect diaphragm function. Seven control and 12 experimental male Sprague-Dawley rats were studied. Six experimental animals were subjected to resistive breathing (RB) alone and six animals received 15 min of mechanical ventilatory support (MV) after the resistive breathing period. Inspiratory resistance was adjusted to maintain airway opening pressure at 70% maximum in both groups until exhaustion. Diaphragm samples were obtained for analysis of thiobarbituric acid-reactive substances (TBAR), reduced glutathione (GSH), and glutathione disulfide (GSSG). In vitro isometric contraction times, twitch (Pt) tension and maximum tetanic (Po) tension, force-frequency curves, fatigue index, and recovery index were measured. In RB and MV compared with controls, there were significant decreases in Pt and Po. Diaphragm TBAR concentrations were increased in MV compared with controls or RB. GSSG-to-total glutathione ratio was increased in RB and MV compared with controls. Production of free radicals during RB and MV may represent an important mechanism of diaphragmatic injury that could contribute to the decline in contractility.

Airway Resistance↗
PubMed1992

Ventilation-perfusion inequalities during graft rejection in patients undergoing single lung transplantation for primary pulmonary hypertension.

We report herein data on single lung transplant (SLT) recipients with primary pulmonary hypertension (PPH). One patient did well following surgery but died on the 30th postoperative day due to cytomegalovirus pneumonia. The remaining two patients initially did well with unlimited exercise tolerance following transplantation, but then developed marked dyspnea on exertion and hypoxemia on postoperative days 144 and 120, respectively. Pulmonary function testing showed marked deterioration of function and transbronchial lung biopsy specimens revealed acute graft rejection in one patient and evidence of chronic graft rejection in the second patient. Quantitative ventilation-perfusion lung scanning demonstrated a marked decrease in ventilation to the transplanted lung in both cases associated with only a mild decrease in perfusion. This V/Q mismatch resulted in markedly decreased arterial oxygen saturations, widened alveolar-arterial oxygen gradients, and clinically debilitating dyspnea. We conclude that rejection may result in significant V/Q mismatch and hypoxemia in PPH patients undergoing SLT, which may limit the use of this specific type of surgery for PPH.

Female↗
PubMed1992

The technique of fiberoptic bronchoscopy. Diagnostic and therapeutic uses in intubated, ventilated patients.

Fiberoptic bronchoscopy has a variety of applications in the intensive care unit. This procedure, which can be done at the patient's bedside, can be used to clear excess secretions; check the position of, or replace, an endotracheal tube; identify areas of active bleeding; diagnose opportunistic infections; and evaluate obstructive airway lesions. Before the bronchoscope is inserted, antisialagogues, anxiolytics, and topical anesthetics are administered along with supplemental oxygen. In intubated, ventilated patients, a fiberoptic bronchoscope may be passed through a swivel adapter to prevent loss of the delivered oxygen and tidal volume. Cardiac arrhythmias and hypoxemia are among the most common complications.

Airway Obstruction↗